Validation and clinical implementation of an accurate Monte Carlo code for pencil beam scanning proton therapy.

Monte Carlo (MC)-based dose calculations are generally superior to analytical dose calculations (ADC) in modeling the dose distribution for proton pencil beam scanning (PBS) treatments. The purpose of this paper is to present a methodology for commissioning and validating an accurate MC code for PBS utilizing a parameterized source model, including an implementation of a range shifter, that can independently check the ADC in commercial treatment planning system (TPS) and fast Monte Carlo dose calculation in opensource platform (MCsquare). The source model parameters (including beam size, angular divergence and energy spread) and protons per MU were extracted and tuned at the nozzle exit by comparing Tool for Particle Simulation (TOPAS) simulations with a series of commissioning measurements using scintillation screen/CCD camera detector and ionization chambers. The range shifter was simulated as an independent object with geometric and material information. The MC calculation platform was validated through comprehensive measurements of single spots, field size factors (FSF) and three-dimensional dose distributions of spread-out Bragg peaks (SOBPs), both without and with the range shifter. Differences in field size factors and absolute output at various depths of SOBPs between measurement and simulation were within 2.2%, with and without a range shifter, indicating an accurate source model. TOPAS was also validated against anthropomorphic lung phantom measurements. Comparison of dose distributions and DVHs for representative liver and lung cases between independent MC and analytical dose calculations from a commercial TPS further highlights the limitations of the ADC in situations of highly heterogeneous geometries. The fast MC platform has been implemented within our clinical practice to provide additional independent dose validation/QA of the commercial ADC for patient plans. Using the independent MC, we can more efficiently commission ADC by reducing the amount of measured data required for low dose "halo" modeling, especially when a range shifter is employed.

A benchmarking method to evaluate the accuracy of a commercial proton monte carlo pencil beam scanning treatment planning system.

AcurosPT is a Monte Carlo algorithm in the Eclipse 13.7 treatment planning system, which is designed to provide rapid and accurate dose calculations for proton therapy. Computational run-time in minimized by simplifying or eliminating less significant physics processes. In this article, the accuracy of AcurosPT was benchmarked against both measurement and an independent MC calculation, TOPAS. Such a method can be applied to any new MC calculation for the detection of potential inaccuracies. To validate multiple Coulomb scattering (MCS) which affects primary beam broadening, single spot profiles in a Solidwater® phantom were compared for beams of five selected proton energies between AcurosPT, measurement and TOPAS. The spot Gaussian sigma in AcurosPT was found to increase faster with depth than both measurement and TOPAS, suggesting that the MCS algorithm in AcurosPT overestimates the scattering effect. To validate AcurosPT modeling of the halo component beyond primary beam broadening, field size factors (FSF) were compared for multi-spot profiles measured in a water phantom. The FSF for small field sizes were found to disagree with measurement, with the disagreement increasing with depth. Conversely, TOPAS simulations of the same FSF consistently agreed with measurement to within 1.5%. The disagreement in absolute dose between AcurosPT and measurement was smaller than 2% at the mid-range depth of multi-energy beams. While AcurosPT calculates acceptable dose distributions for typical clinical beams, users are cautioned of potentially larger errors at distal depths due to overestimated MCS and halo implementation.

Use of a novel two-dimensional ionization chamber array for pencil beam scanning proton therapy beam quality assurance.

The need to accurately and efficiently verify both output and dose profiles creates significant challenges in quality assurance of pencil beam scanning (PBS) proton delivery. A system for PBS QA has been developed that combines a new two-dimensional ionization chamber array in a waterproof housing that is scanned in a water phantom. The MatriXX PT has the same detector array arrangement as the standard MatriXX(Evolution) but utilizes a smaller 2 mm plate spacing instead of 5mm. Because the bias voltage of the MatriXX PT and Evolution cannot be changed, PPC40 and FC65-G ionization chambers were used to assess recombination effects. The PPC40 is a parallel plate chamber with an electrode spacing of 2mm, while the FC65-G is a Farmer chamber FC65-G with an electrode spacing of 2.8 mm. Three bias voltages (500, 200, and 100 V) were used for both detectors to determine which radiation type (continuous, pulse or pulse-scanned beam) could closely estimate Pion from the ratios of charges collected. In comparison with the MatriXX(Evolution), a significant improvement in measurement of absolute dose with the MatriXX PT was observed. While dose uncertainty of the MatriXX(Evolution) can be up to 4%, it is < 1% for the MatriXX PT. Therefore the MatriXX(Evolution) should not be used for QA of PBS for conditions in which ion recombination is not negligible. Farmer chambers should be used with caution for measuring the absolute dose of PBS beams, as the uncertainty of Pion can be > 1%; chambers with an electrode spacing of 2 mm or smaller are recommended.

Practical considerations in the calibration of CT scanners for proton therapy.

Treatment planning systems for proton therapy require a CT calibration curve relating Hounsfield units to proton stopping powers. An understanding of the accuracy of this curve, together with its limitations, is of utmost importance because the calibration underpins the calculated dose distribution of every patient preparing to undergo proton therapy, independent of delivery technique. The most common approach to the calibration is the stoichiometric method, which is well-defined and, in principle, straightforward to perform. Nevertheless, care must be taken when implementing it in the clinic in order to avoid introducing proton range uncertainties into treatment plans that are larger than the 3.5% that target margins are typically designed to account for. This work presents a variety of aspects related to the user-specific implementation of the stoichiometric calibration, from both a measurement setup and a data-handling point of view, and evaluates the potential impact of each for treatment planning purposes. We demonstrate that two alternative commercial vendors' tissue phantoms yield consistent results, that variable CT slice thickness is unimportant, and that, for a given cross-sectional size, all phantom data can, with today's state-of-the-art beam hardening-related artifact reduction software, be acquired quickly and easily with a single scan, such that the resulting curve describes the calibration well at different positions across the imaging plane. We also show that one should be cautious of using metals in the calibration procedure and of using a single curve for anatomical sites differing widely in size. Further, we suggest that the quality of the parametric fit to the measurement data can be improved by performing a constrained, weighted linear regression. These observations, based on the 40 separate curves that were calculated, should help the medical physicist at any new proton therapy facility in deciding which considerations are worth particular attention.

Implementation of an improved dose-per-MU model for double-scattered proton beams to address interbeamline modulation width variability.

Because treatment planning systems (TPSs) generally do not provide monitor units (MUs) for double-scattered proton plans, models to predict MUs as a function of the range and the nominal modulation width requested of the beam delivery system, such as the one developed by the MGH group, have been proposed. For a given nominal modulation width, however, the measured modulation width depends on the accuracy of the vendor's calibration process and may differ from this nominal value, and also from one beamline to the next. Although such a difference can be replicated in our TPS, the output dependence on range and modulation width for each beam option or suboption has to be modeled separately for each beamline in order to achieve maximal 3% inaccuracy. As a consequence, the MGH output model may not be directly transferable. This work, therefore, serves to extend the model to more general clinic situations. In this paper, a parameterized linear-quadratic transformation is introduced to convert the nominal modulation width to the measured modulation width for each beam option or suboption on a per-beamline basis. Fit parameters are derived for each beamline from measurements of 60 reference beams spanning the minimum and maximum ranges, and modulation widths from 2 cm to full range per option or suboption. Using the modeled modulation width, we extract the MGH parameters for the output dependence on range and modulation width. Our method has been tested with 1784 patient-specific fields delivered across three different beamlines at our facility. For these fields, all measured outputs fall within 3%, and 64.4% fall within 1%, of our model. Using a parameterized linear-quadratic modulation width, MU calculation models can be established on a per-beamline basis for each double scattering beam option or suboption.

Comparison of secondary neutron dose in proton therapy resulting from the use of a tungsten alloy MLC or a brass collimator system.

PURPOSE: To apply the dual ionization chamber method for mixed radiation fields to an accurate comparison of the secondary neutron dose arising from the use of a tungsten alloy multileaf collimator (MLC) as opposed to a brass collimator system for defining the shape of a therapeutic proton field. METHODS: Hydrogenous and nonhydrogenous ionization chambers were constructed with large volumes to enable measurements of absorbed doses below 10(-4) Gy in mixed radiation fields using the dual ionization chamber method for mixed-field dosimetry. Neutron dose measurements were made with a nominal 230 MeV proton beam incident on a closed tungsten alloy MLC and a solid brass block. The chambers were cross-calibrated against a (60)Co-calibrated Farmer chamber in water using a 6 MV x-ray beam and Monte Carlo simulations were performed to account for variations in ionization chamber response due to differences in secondary neutron energy spectra. RESULTS: The neutron and combined proton plus γ-ray absorbed doses are shown to be nearly equivalent downstream from either a closed tungsten alloy MLC or a solid brass block. At 10 cm downstream from the distal edge of the collimating material the neutron dose from the closed MLC was (5.3 ± 0.4) × 10(- 5) Gy/Gy. The neutron dose with brass was (6.4 ± 0.7) × 10(- 5) Gy/Gy. Further from the secondary neutron source, at 50 cm, the neutron doses remain close for both the MLC and brass block at (6.9 ± 0.6) × 10(- 6) Gy/Gy and (6.3 ± 0.7) × 10(- 6) Gy/Gy, respectively. CONCLUSIONS: The dual ionization chamber method is suitable for measuring secondary neutron doses resulting from proton irradiation. The results of measurements downstream from a closed tungsten alloy MLC and a brass block indicate that, even in an overly pessimistic worst-case scenario, secondary neutron production in a tungsten alloy MLC leads to absorbed doses that are nearly equivalent to those seen from brass collimators. Therefore, the choice of tungsten alloy in constructing the leaves of a proton MLC is appropriate, and does not lead to a substantial increase in the secondary neutron dose to the patient compared to that generated in a brass collimator.

The Promise of Proton Therapy for Central Nervous System Malignancies.

Radiation therapy plays a significant role in management of benign and malignant diseases of the central nervous system. Patients may be at risk of acute and late toxicity from radiation therapy due to dose deposition in critical normal structures. In contrast to conventional photon delivery techniques, proton therapy is characterized by Bragg peak dose deposition which results in decreased exit dose beyond the target and greater sparing of normal structure which may reduce the rate of late toxicities from treatment. Dosimetric studies have demonstrated reduced dose to normal structures using proton therapy as compared to photon therapy. In addition, clinical studies are being reported demonstrating safety, feasibility, and low rates of acute toxicity. Technical challenges in proton therapy remain, including full understanding of depth of proton penetration and the biological activity in the distal Bragg peak. In addition, longer clinical follow-up is required to demonstrate reduction in late toxicities as compared to conventional photon-based radiation techniques. In this review, we summarize the current clinical literature and areas of active investigation in proton therapy for adult central nervous system malignancies.

AAPM task group 224: Comprehensive proton therapy machine quality assurance.

PURPOSE:  Task Group (TG) 224 was established by the American Association of Physicists in Medicine's Science Council under the Radiation Therapy Committee and Work Group on Particle Beams. The group was charged with developing comprehensive quality assurance (QA) guidelines and recommendations for the three commonly employed proton therapy techniques for beam delivery: scattering, uniform scanning, and pencil beam scanning. This report supplements established QA guidelines for therapy machine performance for other widely used modalities, such as photons and electrons (TG 142, TG 40, TG 24, TG 22, TG 179, and Medical Physics Practice Guideline 2a) and shares their aims of ensuring the safe, accurate, and consistent delivery of radiation therapy dose distributions to patients. METHODS:  To provide a basis from which machine-specific QA procedures can be developed, the report first describes the different delivery techniques and highlights the salient components of the related machine hardware. Depending on the particular machine hardware, certain procedures may be more or less important, and each institution should investigate its own situation. RESULTS:  In lieu of such investigations, this report identifies common beam parameters that are typically checked, along with the typical frequencies of those checks (daily, weekly, monthly, or annually). The rationale for choosing these checks and their frequencies is briefly described. Short descriptions of suggested tools and procedures for completing some of the periodic QA checks are also presented. CONCLUSION:  Recommended tolerance limits for each of the recommended QA checks are tabulated, and are based on the literature and on consensus data from the clinical proton experience of the task group members. We hope that this and other reports will serve as a reference for clinical physicists wishing either to establish a proton therapy QA program or to evaluate an existing one.

Ex vivo validation of a stoichiometric dual energy CT proton stopping power ratio calibration.

A major source of uncertainty in proton therapy is the conversion of Hounsfield unit (HU) to proton stopping power ratio relative to water (SPR). In this study, we measured and quantified the accuracy of a stoichiometric dual energy CT (DECT) SPR calibration. We applied a stoichiometric DECT calibration method to derive the SPR using CT images acquired sequentially at [Formula: see text] and [Formula: see text]. The dual energy index was derived based on the HUs of the paired spectral images and used to calculate the effective atomic number (Z eff), relative electron density ([Formula: see text]), and SPRs of phantom and biological materials. Two methods were used to verify the derived SPRs. The first method measured the sample's water equivalent thicknesses to deduce the SPRs using a multi-layer ion chamber (MLIC) device. The second method utilized Gafchromic EBT3 film to directly compare relative ranges between sample and water after proton pencil beam irradiation. Ex vivo validation was performed using five different types of frozen animal tissues with the MLIC and three types of fresh animal tissues using film. In addition, the residual ranges recorded on the film were used to compare with those from the treatment planning system using both DECT and SECT derived SPRs. Bland-Altman analysis indicates that the differences between DECT and SPR measurement of tissue surrogates, frozen and fresh animal tissues has a mean of 0.07% and standard deviation of 0.58% compared to 0.55% and 1.94% respectively for single energy CT (SECT) and SPR measurement. Our ex vivo study indicates that the stoichiometric DECT SPR calibration method has the potential to be more accurate than SECT calibration under ideal conditions although beam hardening effects and other image artifacts may increase this uncertainty.

Validation and application of a fast Monte Carlo algorithm for assessing the clinical impact of approximations in analytical dose calculations for pencil beam scanning proton therapy.

PURPOSE: Monte Carlo (MC) dose calculation is generally superior to analytical dose calculation (ADC) used in commercial TPS to model the dose distribution especially for heterogeneous sites, such as lung and head/neck patients. The purpose of this study was to provide a validated, fast, and open-source MC code, MCsquare, to assess the impact of approximations in ADC on clinical pencil beam scanning (PBS) plans covering various sites. METHODS: First, MCsquare was validated using tissue-mimicking IROC lung phantom measurements as well as benchmarked with the general purpose Monte Carlo TOPAS for patient dose calculation. Then a comparative analysis between MCsquare and ADC was performed for a total of 50 patients with 10 patients per site (including liver, pelvis, brain, head-and-neck, and lung). Differences among TOPAS, MCsquare, and ADC were evaluated using four dosimetric indices based on the dose-volume histogram (target Dmean, D95, homogeneity index, V95), a 3D gamma index analysis (using 3%/3 mm criteria), and estimations of tumor control probability (TCP). RESULTS: Comparison between MCsquare and TOPAS showed less than 1.8% difference for all of the dosimetric indices/TCP values and resulted in a 3D gamma index passing rate for voxels within the target in excess of 99%. When comparing ADC and MCsquare, the variances of all the indices were found to increase as the degree of tissue heterogeneity increased. In the case of lung, the D95s for ADC were found to differ by as much as 6.5% from the corresponding MCsquare statistic. The median gamma index passing rate for voxels within the target volume decreased from 99.3% for liver to 75.8% for lung. Resulting TCP differences can be large for lung (≤10.5%) and head-and-neck (≤6.2%), while smaller for brain, pelvis and liver (≤1.5%). CONCLUSIONS: Given the differences found in the analysis, accurate dose calculation algorithms such as Monte Carlo simulations are needed for proton therapy, especially for disease sites with high heterogeneity, such as head-and-neck and lung. The establishment of MCsquare can facilitate patient plan reviews at any institution and can potentially provide unbiased comparison in clinical trials given its accuracy, speed and open-source availability.

Technical Note: Validation of halo modeling for proton pencil beam spot scanning using a quality assurance test pattern.

PURPOSE: The purpose of this paper is to demonstrate the utility of a comprehensive test pattern in validating calculation models that include the halo component (low-dose tails) of proton pencil beam scanning (PBS) spots. Such a pattern has been used previously for quality assurance purposes to assess spot shape, position, and dose. METHODS: In this study, a scintillation detector was used to measure the test pattern in air at isocenter for two proton beam energies (115 and 225 MeV) of two IBA universal nozzles (UN #1 and UN #2). Planar measurements were compared with calculated dose distributions based on the weighted superposition of location-independent (UN #1) or location-dependent (UN #2) spot profiles, previously measured using a pair-magnification method and between two nozzles. RESULTS: Including the halo component below 1% of the central dose is shown to improve the gamma-map comparison between calculation and measurement from 94.9% to 98.4% using 2 mm/2% criteria for the 115 MeV proton beam of UN #1. In contrast, including the halo component below 1% of the central dose does not improve the gamma agreement for the 115 MeV proton beam of UN #2, due to the cutoff of the halo component at off-axis locations. When location-dependent spot profiles are used for calculation instead of spot profiles at central axis, the gamma agreement is improved from 98.0% to 99.5% using 2 mm/2% criteria. The two nozzles clearly have different characteristics, as a direct comparison of measured data shows a passing rate of 89.7% for the 115 MeV proton beam. At 225 MeV, the corresponding gamma comparisons agree better between measurement and calculation, and between measurements in the two nozzles. CONCLUSIONS: In addition to confirming the primary component of individual PBS spot profiles, a comprehensive test pattern is useful for the validation of the halo component at off-axis locations, especially for low energy protons.

Experimental characterization of two-dimensional spot profiles for two proton pencil beam scanning nozzles.

Dose calculation for pencil beam scanning proton therapy requires accurate measurement of the broad tails of the proton spot profiles for every nozzle in clinical use. By applying a pair/magnification method and merging film data, 200 mm × 240 mm dose kernels extending to 10(-4) of the central spot dose are generated for six selected energies of the IBA dedicated and universal nozzles (DN and UN). One-dimensional, circular profiles up to 100 mm in radius are generated from the asymmetric profiles to facilitate spot profile comparison. For the highest energy, 225 MeV, the output of both the DN and the UN for field sizes from 40 to 200 mm increases in parallel, slowest at the surface (∼1%) and fastest at a depth of 150 mm (∼9%). In contrast, at the lowest energy, 100 MeV, the output of the DN across the same range of field sizes increases 3-4% versus 6-7% for the UN throughout all the depths. The charge deficits in the measured depth-dose of Bragg peaks are similar between the UN and the DN. At 100 MeV, the field size factor difference at the surface between two orientations of a rectangular 40 mm × 200 mm field is 1.4% at isocentre for the DN versus 2% for the UN. Though the one-dimensional distributions are similar for the primary and tail components at different positions, the primary components of the DN spots are more elliptical 270 mm upstream than at isocentre.

Experimentally validated pencil beam scanning source model in TOPAS.

The presence of a low-dose envelope, or 'halo', in the fluence profile of a proton spot can increase the output of a pencil beam scanning field by over 10%. This study evaluated whether the Monte Carlo simulation code, TOPAS 1.0-beta 8, based on Geant4.9.6 with its default physics list, can predict the spot halo at depth in phantom by incorporating a halo model within the proton source distribution. Proton sources were modelled using three 2D Gaussian functions, and optimized until simulated spot profiles matched measurements at the phantom surface out to a radius of 100 mm. Simulations were subsequently compared with profiles measured using EBT3 film in Solidwater® phantoms at various depths for 100, 115, 150, 180, 210 and 225 MeV proton beams. Simulations predict measured profiles within a 1 mm distance to agreement for 2D profiles extending to the 0.1% isodose, and within 1 mm/1% Gamma criteria over the integrated curve of spot profile as a function of radius. For isodose lines beyond 0.1% of the central spot dose, the simulated primary spot sigma is smaller than the measurement by up to 15%, and can differ by over 1 mm. The choice of particle interaction algorithm and phantom material were found to cause ~1 mm range uncertainty, a maximal 5% (0.3 mm) difference in spot sigma, and maximal 1 mm and ~2 mm distance to agreement in isodoses above and below the 0.1% level, respectively. Based on these observations, therefore, the selection of physics model and the application of Solidwater® as water replacement material in simulation and measurement should be used with caution.

Optimization of the modelling of longitudinal dose distributions for double-scattered proton beams in a commercially-available treatment planning system.

The configuration of a treatment planning system (TPS) for double-scattering-based proton therapy requires many user inputs. Most of these are either gathered during the routine collection of commissioning data, or can be supplied by the equipment vendor; however, this is not true of all. In this study we developed a technique both to (a) expedite the extraction of those undetermined TPS parameters related to the range modulator wheels that can only otherwise be obtained by the time-consuming process of trial-and-error, and (b) demonstrate how, for a commonly-employed, commercially-available TPS, the judicious determination of such parameters can be used to optimize the resultant modelling of longitudinal dose distributions delivered by a double scattering proton therapy system. Our technique is simple to implement, robust in nature and also provides insight allowing parameters that must be contrived in that model to be related directly to physical aspects of the beam delivery system.

Experimental characterization of two-dimensional pencil beam scanning proton spot profiles.

Dose calculations of pencil beam scanning treatment plans rely on the accuracy of proton spot profiles; not only the primary component but also the broad tail components. Four films are placed at several locations in air and multiple depths in Solidwater® for six selected energies. The films used for the primary components are exposed to 50-200 MU to avoid saturation; the films used for the tail components are exposed to 800, 8000 and 80,000 MU. By applying a pair/magnification method and merging these data, dose kernels down to 10(-4) of the central spot dose can be generated. From these kernels one can calculate the dose-per-MU for different field sizes and shapes. Measurements agree within 1% of dose-kernel-based calculations for output versus field size comparisons. Asymmetric, comet-shaped profile tails have a bigger impact at superficial depths and low energies: the output difference between two orientations at the surface of a rectangular field of 40 mm×200 mm is about 2% at the isocentre at 100 MeV. Integration of these dose kernels from 0 to 40 mm radius shows that the charge deficit in the Bragg peak chamber varies <2% from entrance to the end of range for energies <180 MeV, but exceeds 5% at 225 MeV.

A novel technique for measuring the low-dose envelope of pencil-beam scanning spot profiles.

To investigate the profile measurement capabilities of an IBA-Dosimetry scintillation detector and to assess its feasibility for determining the low-intensity tails of pencil-beam scanning spots, the responses of the scintillation detector and Gafchromic EBT2 film to a 115 MeV proton spot were measured in-air at the isocenter. Pairs of irradiations were made: one lower-level irradiation insufficient to cause saturation, and one higher-level irradiation which deliberately saturated the central region of the spot, but provided magnification of the tails. By employing the pair/magnification technique, agreement between the film and scintillation detector measurements of the spot profile can be extended from 4% of the central spot dose down to 0.01%. Gamma analysis between these measurements shows 95% and 99% agreement within a ±9 cm bound using criteria of 3 mm/3% and 5 mm/5%, respectively. Above 4%, our 115 MeV proton spot can be well-described by Gaussian function; below 4%, non-Gaussian, diamond-shaped tails predominate.